The effects of Protocadherin 10 on apoptosis and stemness in colorectal cancer
| Autor: | Yu-Lin Hung, 洪佑霖 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Colorectal cancer (CRC) is the third leading cause of cancer death in the United states and Taiwan. Most deaths of CRC are associated with distant metastasis, including liver and lung. Although recent researches have acclaimed that many alternative treatments to attenuate tumor progression, but not always get good prognosis. Therefore, an improved understanding of the molecular mechanism involved in CRC may provide new insights into CRC diagnosis and treatment. In previous studies, we demonstrated that PCDH10 is a crucial tumor suppressor gene in CRC by cell proliferation, anchorage-independent growth, migration and invasion assay in vitro. Moreover, we also performed tumorigenesis and liver metastasis experiments with in vivo xenograft tumor models. The results confirmed that PCDH10 is a CRC-associated tumor suppressor gene. In the study, there are three specific aims. The first was focused on the role of PCDH10 in regulation of apoptosis. The results indicated that PCDH10 increased not only spontaneous apoptosis, but also oxidative stress-induced apoptosis. The second part was focused on the effect of PCDH10 on cancer stemness. The results showed that re-expression of PCDH10 decreased spheroid formation and down-regulated cancer stem cell markers, including CD133, Bmi-1, Nanog and Sox2 in CRC cells. In the third part, we investigated the pathways involved in PCDH10-modulated apoptosis and stemness potential. The results revealed that PCDH10 might down-regulate PI3K/AKT and Sonic Hedgehog signaling pathways to induce apoptosis and inhibit stemness potential. Taken together, we further confirm that PCDH10 plays a crucial role in tumor suppression and disclose the molecular mechanisms regulated by PCDH10. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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